folditfandomcom-20200222-history
Structures of the Protein
'Structures of the Protein. ' 'What does Primary, secondary, therchary, quartiary, structure mean?' A protein has 3 structures and when combined with another protein, even 4 types of structures. The Primary structure is the Amino Acid sequence. AA sequence is important for several reasons, sequence determination is part of molecular pathology, an emerging area of modern medicine. The Secondary structure is the common shapes that occur, alpha helix, beta sheet and the other minor structures that are repeatitive enough to carry a shape. The tertiary is an ensemble of the backbone polypeptide's 3D structure including the disulphide bridge. Quartiary would be multiple polypeptide units interacting. Protein structures in the most basic terms are: 'Primary Structure (PS)' is determined by the sequence of amino acids making up the backbone, not the shape or position of the backbone. 'Secondary Structure (SS)' is the backbone's Spacial arrangements, Alpha Helix, and Beta Sheets that define the shape of the backbone. These are held in shape by hydrogen bonds. This does not include loops because the shapes of the loops are not defined. Super Secondary Strucure (SSS) - is a cluster or pattern in SS (bAb unit) 'Tertiary Structure (TS)' is the position of the protein's amino acid sidechains and the hydrogen bonds that holds the protein together into a completed unit. The structure of the whole protein forms the isosurface. Spacial interaction as whole. Change any of the first 3 structures and you will change the isosurface. 'Quartiery Structure (QS)' is the outside shape of a native protein's isosurface, and how closely it fits into another protein's isosurface. This is how many different whole protein sub-units fit together, like puzzle peices, into larger micro structures. We see this on foldit in Docking, Interface, and Symmetric puzzles, where smaller sub-unit proteins snuggle up close together forming larger structures. Fits like a key in a lock. Multiple polypeptide chain, subunit interaction. 'Secondary Structures of the Protein.' 'The Alpha Helix - Helix' 'The Beta Sheet - Sheet' 'The B-Turn or U-Turns - U-Turn' 'Reactive centers -' Sometimes there are reactive centers that are on the outside of a protein. These may be orange sidechains with yellow balls. The yellow balls indicate that these are exposed hydrophobic side chains. Normally you would want these to be turned inward for a better score. 'Amino Acids' AA(Amino Acid) = The molecular unit in the polypeptide chain. An individual AA is made of a carbonyl and amine group attached to a central tertiary carbon that has either an additional hydrogen atom or arrays of extended sidechain. Some acidic some basic, some polar some non-polar. Some steric. Some aromatic. Each AA has its different configuration. It may varie in its polarity (which attracts water and other polar solvents), its length (stericity), its capabilities for hydrogen bonding, and its aromatic features. Certain AA have a physical structure that makes it best for certain features. For example Leucine zipper - that form bonds between 2 parille helix. Glycine hinge - forms the bend or u turn in loops at the end of the sheets. Internal AA tend to have sidechains that are non-polar. For example: Myoglobin - the Oxygen-carrying protein in red blood cells has an interior that consists almost entirely of nonpolar residues such as leucine, valine, methionine & phenylaniline. Certain amino acids are found more in certain areas of the protein. For example, Proline is found at the bends of folded proteins. Valine, Leucine & Isoleucine are Hydrophobes. Phenylalamine & Tryptophan are Highly hydrophobe. Hydrogen donor: Tryptophan & Arganine. Hydrogen donor & acceptor: Asparagine, Glutamine, Serine, Threomine. pH-dependent hydrogen D or A: Glutamic acid, Tyrosine, Histidine. 'Different types of sidechains' *Aliphatic sidechains: Alanine, Valine, Leucine, Glycine, Proline, Isoleucine *Hydroxyl aliphatic: Serine, Threonine *Aromatic sidechains: Phenylalanine, Tryptophan, Tyrosine *Basic sidechains: Lysine, Histidine, Arginine *Acidic sidechains: Glutamic acid, Aspartic acid *Amide sidechains: Asparagine, Glutamine *Sulfur sidechains: Cysteine, Methionine In the polypeptide chain, the rotation between alpha carbon and nitrogen in the backbone is called Phi Φ, and the rotation between alpha carbon and carbonyl carbon is called psi Ψ. Stetic hyndrance, or clashes, prevent certain angles.These can be seen on the Ramachandran plot. ''GENERAL CHEMISTRY '''- how do protein structures form and why. Lets consider aromacity, hydrogen bonds, steric hyndrance, hydrophobicity, disulfide bridge. 'Aromatics - Aromacity (delocalized pi-bond) Pi-system cluster amongst themselves. Both sulfuric AA (Cysteine & Methionine) are hydrophobic. Glycine is the only optically inactive AA Lysine & Arganine are the positively charged and also have the longest sidechain in all the AAs. Amino Acids start with the amino terminal, not the carboxyl terminal. 'How pH can affect AA' AA with amine (hydrogen donor) or carbonyl (hydrogen acceptor) 'Zwitterions:' AAs work as zwitterions.Zwitterions are dipolar molecules. In this case, the dipolarity is found in the carbonyl (negative) and amine (positive) functional group. 'Disulphide bridges - Disulfide Bond' 'Chemical bond types' 'Covalent bonds ' - A covalent bond is a bond in which 2 atoms are sharing pairs of electrons. the strength of covalent bonds differs, but in general they are stronger than hydrogen bonds, van der waals, and static forces. There are two types of covalent bonds found in proteins The regular covalent bond links each peptide in the polypeptide chain of the protein, and all the bonds within the amino acids. The other is found between the 2 cysteines' sulfur atoms: A disulphide bond. Disulphide are an analog of dioxygen (peroxides) which are known for their weak bonds and are used in chemistry for free-radical reactions. 'Hydrogen bonds ' - Hydrogen bond occurs when 2 atoms are sharing a hydrogen atom. For example in alpha helix and beta sheets, the oxygen atom of a carbonyl group will be the '' hydrogen acceptor'' and the nitrogen of the amine group will be the hydrogen donor. The dipole force is interesting for the "shape" of the hydrogen interaction. Since Oxygen has 2 free electron pairs, it can accept 2 hydrogen for HB. Nitrogen has 1 free pair.Stronger than the regular dipole movement, but weaker than Covalent and Static, being only ~10% as strong as covalent bonds. 'Steric hinderence, Stericity, Van der waals force = Clashes' Is a force of great repulsion when 2 atoms get closer then 3-4 Å apart. This is caused by an overlap of their electron clouds or isosurface The further away, the weaker the force. For example: Carbon to Oxygen (C-O) optimal distance = 3.4 Å, which is the the radii of both (1.4 and 2.0 Å Only about ~1Kcal/mol. Low compared to hydrogen bonds. Which compares to the average thermal energy of molecules @ room temperature ~0.6Kcal/mol Bigger atoms have a larger dispersion force (london force). 'Tempoary fluctuating dipoles' 'Polarity or Electrostatic bond' '- ' Ionic bond, salt linkage, salt bridge, ion pairPolar amino acids tend to attrack water as water is polar. These tend to be on the outside of the protein. 'USEFUL LINKS' *'Helix' more at http://foldit.wikia.com/wiki/Helix *'Sheet' more at http://foldit.wikia.com/wiki/Sheet *'U-turn' more at http://foldit.wikia.com/wiki/U-Turn *'Disulfide bridge' more at http://foldit.wikia.com/wiki/Disulfide_Bridge *'Glycine hinge' more at http://foldit.wikia.com/wiki/Glycine_Hinge *'hydrophobicity' more at http://foldit.wikia.com/wiki/Hydrophobicity *'hydrogen bonds' more at http://foldit.wikia.com/wiki/Hydrogen_bond http://foldit.wikia.com/wiki/Hydrogen_Bonding*'Disulfide bridge' more at http://foldit.wikia.com/wiki/Disulfide_Bridge *'Steric hyndrance' more at http://en.wikipedia.org/wiki/Steric_effects *'Aromatic interaction' more at http://en.wikipedia.org/wiki/Aromatic_interaction Hinge prediction http://stonehinge.bmb.msu.edu/ http://molmovdb.org/cgi-bin/submit-flexoracle.cgihttp://rigidfinder.molmovdb.org/ Protein motion http://rigidfinder.molmovdb.org/http://molmovdb.org/cgi-bin/movie.cgi More Techniques at > The Foldit Labs Category:Itskimo strategy